Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation

Alari-Pahissa, Elisenda; Federico-Vega, Judith; Ataya Fernández, Michelle, 1993-; Buxeda, Anna; Bello-Rico, Víctor; Gimeno, Javier; Yélamos López, José; Altadill, Mireia; Sanz-Ureña, Sara; Riera, Marta; Burballa Tàrrega, Carla, 1988-; Chamoun, Betty Odette; Pérez-Sáez, María José; Redondo Pachón, María Dolores; Vilches, Carlos; Crespo Barrio, Marta; López-Botet, M. (Miguel)

Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation

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dc.contributor.author Alari-Pahissa, Elisenda
dc.contributor.author Federico-Vega, Judith
dc.contributor.author Ataya Fernández, Michelle, 1993-
dc.contributor.author Buxeda, Anna
dc.contributor.author Bello-Rico, Víctor
dc.contributor.author Gimeno, Javier
dc.contributor.author Yélamos López, José
dc.contributor.author Altadill, Mireia
dc.contributor.author Sanz-Ureña, Sara
dc.contributor.author Riera, Marta
dc.contributor.author Burballa Tàrrega, Carla, 1988-
dc.contributor.author Chamoun, Betty Odette
dc.contributor.author Pérez-Sáez, María José
dc.contributor.author Redondo Pachón, María Dolores
dc.contributor.author Vilches, Carlos
dc.contributor.author Crespo Barrio, Marta
dc.contributor.author López-Botet, M. (Miguel)
dc.date.accessioned 2025-07-23T07:11:23Z
dc.date.available 2025-07-23T07:11:23Z
dc.date.issued 2025
dc.description.abstract Inhibitory killer cell immunoglobulin-like receptors (iKIRs) are randomly expressed by natural killer (NK) cell subsets and recognize motifs shared by HLA class-I (HLA-I) allotypes. Such interactions prevent NK cell autoreactivity while enhancing their response against cells lacking those HLA-I molecules (missing self), a situation defined in transplantation as iKIR-HLA-I mismatch (iKIR-MM), whose genotypic prediction has been associated with microvascular inflammation (MVI). Herein, we compared iKIR-MM in kidney transplant recipients with MVI ≥2 (n = 19) and controls with MVI ≤1 (n = 36). In parallel to genetic analysis of iKIR-MM, which was more frequent in MVI ≥2 patients, putative alloreactive iKIR-MM NK cells were defined by flow cytometry as NKG2A(-) cells bearing self-specific but lacking donor-specific iKIR. Although iKIR-MM NK cells were detected in both groups, their pretransplant numbers were higher in MVI ≥2 patients (median = 11.02, interquartile range = 0-58.31 vs median = 0, interquartile range = 0-9.46), especially in the presence of donor-specific antibodies or C4d, and correlated with MVI grade. Pretransplant, a subset of MVI ≥2 patients showed high proportions and numbers of oligoclonal iKIR-MM NK cells, which displayed an NKG2C(+) adaptive phenotype associated with cytomegalovirus infection. This pilot study provides a novel perspective on the contribution of iKIR-MM NK cells to MVI, with potential practical implications.
dc.description.sponsorship J.F.V. had support from a grant awarded by the Catalan Transplantation Foundation. This study was supported by grants: “PI20/00090” and “PI23/00061”, funded by Instituto de Salud Carlos III (ISCIII) FIS and co-funded by the European Union (EU-FEDER); “PID2019-110609RB-C21” and “PID2019-110609RB-C22” (funded by Agencia Estatal de Investigación and cofunded by EU-FEDER; “P105/U/2018” (Fundació la Marató de TV3); “RD21/0005/0022” (National Network for Kidney Research RICORS2024, co-funded by Spanish Ministry of Health-ISCIIII and European Union-NextGenerationEU), Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS 2040-Renal (RD24/0004/0003) funded by European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR), and a 2023 Nephrology Research grant (Spanish Society of Nephrology S.E.N).
dc.format.mimetype application/pdf
dc.identifier.citation Alari-Pahissa E, Federico-Vega J, Ataya M, Buxeda A, Bello-Rico V, Gimeno J, et al. Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation. Am J Transplant. 2025 Aug;25(8):1657-69. DOI: 10.1016/j.ajt.2025.04.024
dc.identifier.doi http://dx.doi.org/10.1016/j.ajt.2025.04.024
dc.identifier.issn 1600-6135
dc.identifier.uri http://hdl.handle.net/10230/70976
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Am J Transplant. 2025 Aug;25(8):1657-69
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C21
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22
dc.rights © 2025 The Authors. Published by Elsevier Inc. on behalf of American Society of Transplantation & American Society of Transplant Surgeons. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword KIR-HLA-I mismatch
dc.subject.keyword Antibody-mediated rejection
dc.subject.keyword Killer cell immunoglobulin-like receptors
dc.subject.keyword Microvascular inflammation
dc.subject.keyword Natural killer cells
dc.subject.keyword Renal transplant
dc.title Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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